One of the foremost causes of sudden death is ventricular fibrillation accompanying myocardial infarction. The purpose of these investigations is to obtain direct electrophysiological evidence for the mechanisms responsible for the initiation and maintenance of ventricular fibrillation, and for ventricular defibrillation. Both intracellular microelectrode and extracellular bipolar recording and stimulation techniques will be utilized. A hybrid computer system permits on-line analysis of data. Numerous conflicting reports have appeared as to the effects of various cardiac drugs and other perturbation upon the ventricular fibrillation threshold (VFT) measured as the minimum current required to initiate ventricular fibrillation. A reliable VFT technique has been developed in this lab which will be used to study the interactions of combinations of various cardiac drugs (i.e. combinations of drugs within the same class vs. combinations of a Class I plus Class II drug), electrolyte imbalances, acid-base changes, rate and rhythm changes, blood pressure changes, etc. Studies will be performed to determine what drugs and factors favor cessation of fibrillation. Microelectrode studies will include analyzing the supernormal phase of excitability in atrial, ventricle and specialized AV conduction tissue using a method for stimulating and recording through a single microelectrode. Also, the biophysical properties of subthreshold local responses, after potentials and oscillations will be analyzed from the standpoint of the initiation and maintenance of VF. In summary, the porposed studies should provide new direct electrophysiological information on the processes responsible for the initiation of fibrillation and for defibrillation.